Research Gives Hope Against Rare Muscle Disorder

WEDNESDAY, June 20 (HealthDay News) -- Research in mice may help in the development of new treatments for a rare degenerative muscle disease called hereditary inclusion body myopathy (HIBM).

The same insights might also help people battling certain kidney disorders, researchers say.

Most people with HIBM develop symptoms in their early 20s and are confined to a wheelchair by the time they're in their 40s. The disease causes a progressive weakening of arm, hand, leg and core body muscles.

HIBM is thought to be caused by a mutation in the GNE gene that affects production of sialic acid, a sugar that's important to muscle development and kidney function. Currently, there is no treatment for HIBM.

In this study, published in the June issue of the Journal of Clinical Investigation, the researchers wanted to test whether a compound called N-acetylmannosamine (ManNAc), a sugar that's naturally converted into sialic acid, could reduce HIBM-related muscle weakness in mice with a specific GNE mutation. This defect typically causes a form of HIBM in Iranian-Jewish families.

However, the scientists were surprised to find that, instead of developing adult-onset muscle weakness, the mice developed a kidney condition that caused them to die within a few days of birth.

On the other hand, when pregnant mice were given ManNAc in their diets, there was an improvement in sialic acid production in the fetuses, and the baby mice were born with markedly improved kidneys.

In addition, none of the offspring born to mice that were given ManNAc during pregnancy developed the HIBM-like muscle weakness.

"We were surprised that the HIBM mutation had such a detrimental impact on kidney function in the [genetically engineered] mice," team leader Marjan Huizing, an associate investigator in the Medical Genetics Branch at the U.S. National Human Genome Research Institute (NHGRI), said in a prepared statement.

"Structural elements in the kidney that are important for filtering waste from the blood in these animals were severely impaired, and we linked this to the sialic acid deficiency. This outcome demonstrates the significance of the ability of the body to synthesize sialic acid for kidney development and function," Huizing said.

Study co-author and NHGRI Clinical Director Dr. William Gahl said that, with respect to HIBM, "we are hoping that humans with the same genetic mutation as our mouse model will also respond to ManNAc."

A clinical trial of ManNAc for HIBM is expected to begin later this year.